AIDS disease first detected in significant numbers of patients in 1981, named in 1982 and characterized in 1983 in France and in 1984 in the U.S. is a virus that invades the genetic material of immunologically competent cells destroying them and ultimately killing 100% of all victims who die of opportunistic diseases such as Kaposi's sarcoma and pneumocystis carinii pneumonia. The virus is thought to reside largely within the helper T cell of the blood and to compel rapid multiplication of the virus by the genetic apparatus of this and similar immunocompetent cells which ultimately die and release more HIV virus to invade other cells. The incubation time is now thought to be 5 to 7 years with the manifestation of the disease initially signalled by the appearance of AIDS positive antibodies. This is generally followed by various signs of malaise including weakness, reduction of appetite, severe weight loss and increasing susceptibility to infections and viral invasions that are normally prevented or defeated by the competent immune system of the uninfected healthy individual. Death usually ensues within eighteen months to several years after the appearance of symptoms, although there have been some notable exceptions, and current drug therapy appears to be extending survival time to a limited extent.
The approach to therapy has gone in several directions. Naturally, the initial thrust was directed towards the symptomatic treatment of the opportunistic diseases that were the cause of death at the terminal stages. These attempts included the use of anticancer drugs for the Kaposi's sarcoma and a variety of antibiotic or antiviral drugs for the pneumocystis carinii. A more recent approach has included the development of several drugs designed to block the replication of the virus in the interior of the cell and AZT and DDI are two of the more successful of these attempts. AZT is now being used extensively. It is very expensive, quite toxic to bone marrow (and because of this may not be used in all patients) and seems only to retard the progression of the disease by slowing the multiplication of the HIV virus, but it does not reverse the process. DDI seems to show much greater promise and early reports include evidence of reduction of viral titers as well as weight gain and reappearance of vitality in some patients.
Another approach to therapy has involved the attempt to develop a vaccine for the virus. Early efforts based on a variety of approaches involving the use of a portion of the outer protein coat as an antigen to produce antibodies have been unsuccessful because the complexity of the glycoprotein does not encourage extensive antibody production. Also, since the AIDS virus resides within the interior of the cell access is limited in infected cells and in other cases the virus appears to be capable of mutation that allows avoidance or escape from the antibody that would destroy it. Currently a number of other approaches are being attempted that incorporate a variety of recombinant techniques. These involve replication of portions of viral proteins that might be used to stimulate the immune system, inserting the gene for one of the AIDS antigen glycoproteins into vaccinia virus, the use of anti-idiotypes to stimulate the immune system in an identical way as the AIDS virus without the immune cell toxicity and creation of copies of the helper T cell receptor that AIDS virus attaches to as a strategy to tie up and titrate the virus before it attaches to susceptible cells. Finally, there are the older more traditional approaches that utilizes whole killed AIDS virus to stimulate the immune system.
In general, all of these approaches involve one of three regimes: blockade of replication of the AIDS virus, or its immunological destruction by antibodies, or its sequestration by receptor duplicates and perhaps eventually blockade of attachment to actual T cell receptors. All of these approaches however, do not address what could be an immediate approach to reduction of the body burden of the virus regardless of the phase of infection or the stage of progression of the disease. In fact, the failure of several therapeutic approaches when tried in patients, even though they showed so much promise in vitro, have been attributed to the overwhelming amount of virus that exists in infected humans or the animal model in comparison to the amount present in tissue culture testing. There is very little doubt that the effectiveness of any of the above approaches, particularly the use of antivirals to block replication of the virus, would be enhanced and the probability of success heightened if the amount of virus in the body could be drastically diminished.
In fact, a recent report in SCIENCE (July 21, 1989) has demonstrated that the body burden of AIDS virus is far greater than suspected earlier, namely that at least one in one hundred white blood cells (CD4 positive T4 cells) are infected rather than one in ten thousand, an increase of one hundred fold. This appears to be an extremely high number of infected cells as stated by the authors who performed the work. This publication also indicates that there is ten times higher level of rapidly replicating AIDS virus in patients then was previously thought.